RENIN-ANGIOTENSIN SYSTEM AND ALDOSTERONE REGULATION

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The purpose of this project is to analyze physiological and pathological aspects of the renin angiotensin system, including the effects of AII in circulatory homeostasis, pituitary and gonadal function. All mediates the increase in aldosterone secretion during sodium restriction, but the adrenal effects of the peptide are dependent on the sensitivity of the glomulosa zone to AII. Previous studies in the rat have demonstrated that the adrenal responsiveness to AII depends on the trophic effects of the peptide and the modulatory effect of other regulators such as dopamine, atrial natriuretic factor (ANF) and somatostatin (SRIF). Studies on the adrenal effects of SRIF were extended to the primate. SRIF like immunoactivity was identified in monkey and human adrenal cortex and the peptide was found to preferentially inhibit AII stimulated aldosterone production in isolated monkey adrenal cells, suggesting that SRIF has a role in the control of aldosterone secretion in primates. Studies on the mechanisms of action of aldosterone regulators were focused on the effects ANF in the adrenal and pituitary. ANF was a potent stimulatory cGMP production but the cyclic nucleotide had no inhibitory effect on steroidogenesis. ANF inhibited aldosterone secretion without affecting AII induced increases in cytosolic calcium or phospholipid turnover. Arachidonic acid inhibited aldosterone secretion with characteristics similar to those of ANF suggesting that arachidonic acid metabolism may be involved in the effects of ANF. In pituitary cells ANF stimulated cGMP production without affecting basal or stimulated pituitary hormone production. In the gonads AII receptors are present in Leydig cells in the testes and granulosa and luteal cells to the ovary of rat and primates. In the ovary AII receptor activation by coupled to calcium mobilization with increases in cytosolic calcium. The presence of AII receptors in the testes and ovaries suggest a role for the peptide in the regulation of gonadal function.